Recapitulating native retina environment is crucial in isolation and culturing of retina photoreceptors (PRs). To date, maturation of PRs remains incomprehensible in vitro. Here we present a strategy of integrating the physical and chemical signals through 3D-bioprinting of hyaluronic acid (HA) hydrogels and co-differentiation of retinal progenitor cells (RPCs) into PRs with the support of retinal-pigment epithelium (RPEs). To mimic the native environment during retinal development, we chemically altered the functionalization of HA hydrogels to match the compressive modulus of HA hydrogels with native retina. RPEs were incorporated in the culturing system to support the differentiation due to their regeneration capabilities. We found that HA with a specific functionalization can yield hydrogels with compressive modulus similar to native retina. This hydrogel is also suitable for 3D bioprinting of retina structure. The results from cell study indicated that derivation of PRs from RPCs was improved in the presence of RPEs.
Keywords: 3D bioprinting; Compressive modulus; Hyaluronic acid; Photoreceptors; Retina; Retinal-pigment epithelium.